Renal function in gout: II. Effect of uric acid loading on renal excretion of uric acid

Abstract

Thirteen non-gouty and twelve gouty men to whose regular diet was added 4 gm. of ribonucleic acid (RNA) daily, developed increases in plasma uric acid, urinary excretion of uric acid and derived parameters, without significant differences in the mean increments in non-gouty and gouty subjects. Ten non-gouty and seventeen gouty men were given intravenous injections of 1.1 to 2.5 gm. uric acid to impose even greater demands upon the tubular mechanisms for transfer of uric acid, and again the mean increments in the urinary excretion of uric acid and uric acid clearance in non-gouty and gouty subjects were indistinguishable. Pyrazinoic acid, a potent inhibitor of tubular secretion of uric acid, was found to suppress the urinary elimination of rapidly infused uric acid in gouty and non-gouty subjects alike.The data indicate that gouty subjects can excrete large extraneous loads of uric acid with as much facility as normal man, and support the view that this obtains also for the usually smaller and more slowly delivered endogenous uric acid loads natural to gout. The results thus argue against any intrinsic defect, peculiar to gout, in the renal mechanisms for excretion of uric acid.Briefly reviewed is the evidence that tubular secretion of uric acid occurs in non-gouty and gouty man, indeed that virtually all the uric acid appearing in the urine ordinarily derives from tubular secretion, hence virtually all the filtered uric acid ordinarily must be reabsorbed. It is pointed out that in this version of the filtration-reabsorption-secretion hypothesis there need be no simple relationship between the filtered and excreted uric acid, a dissociation found in gout that has been interpreted by others as indicating a primary tubular defect in transfer of uric acid. The implications of the filtration-reabsorption-secretion hypothesis in respect to other aspects of the renal regulation of uric acid are discussed in relation to excretion of uric acid in normal and gouty man under natural and artificial conditions of uric acid loading.The present study, limited to over-all clearances, gives no information as to the precise mechanisms or quantitative aspects of tubular secretion of uric acid in normal or gouty man, nor does it explain just how renal excretion of large and rapidly imposed uric acid loads is regulated.